Nephrotic syndrome redux.

Redux: brought back, resurgent (Wikipedia free dictionary). This essay traces the history of the concepts that led to the usage of the term 'nephrotic syndrome' beginning ∼90 years ago. We then examined the various definitions used for this syndrome and modified them to conform to contemporary standards. Remarkably, only minor modifications were required. This analysis of a common clinical entity may be helpful in ensuring appropriate evaluation of patients suffering from nephrotic syndrome and nephrotic-range proteinuria.

The death of Wolfgang Amadeus Mozart: an epidemiologic perspective.

The early death of the composer Wolfgang Amadeus Mozart on 5 December 1791 has fascinated the world for more than 2 centuries. It has been suggested that his final illness was caused by poisoning, renal failure, Henoch-Schönlein purpura, trichinosis, and many other conditions. The official daily register of deaths in Mozart's Vienna was evaluated to provide an epidemiologic framework into which the observations of contemporary witnesses of his death can be integrated. All recorded deaths in Vienna during November and December 1791 and January 1792 were analyzed, together with the corresponding periods in 1790 to 1791 and 1792 to 1793. The deaths of 5011 adults (3442 men, 1569 women) were recorded over these periods. The mean ages of death were 45.5 years (SD, 18.5) for men and 54.5 years (SD, 19.9) for women. Tuberculosis and related conditions accounted for the highest number of deaths; cachexia and malnutrition ranked second, and edema was the third most common cause. According to eyewitness accounts, the hallmark of Mozart's final disease was severe edema. Deaths from edema were markedly increased among younger men in the weeks surrounding Mozart's death compared with the previous and following years. This minor epidemic may have originated in the military hospital. Our analysis is consistent with Mozart's last illness and death being due to a streptococcal infection leading to an acute nephritic syndrome caused by poststreptococcal glomerulonephritis. Scarlet fever, which represents the same underlying disease from an etiologic perspective, is a less likely possibility.

[History of nephrotic syndrome].

The history of nephrotic syndrome can go back to beginning of the era. In old Alexandria, urine was conceived to be produced in kidneys. In 1827, Bright classified diseases with proteinuria into three categories, and lipoid nephrosis seemed to be included in group 1. Mechanisms of urinary protein leakage have been in great controvesies, and nowadays defects of slit-membrane protein are supposed to play important roles. In the middle of the 20th centuries, electron microscopy and renal biopsy technique were adopted in practical use. Since then, the treatment and research of nephrotic syndrome have been remarkably progressed. Clinical strategies including diet therapy, immuno-suppressive and antihypertensive drugs and other modalities have improved the prognosis of nephrotic syndrome.

Edmund Randerath (1899-1961): experimental proof for the glomerular origin of proteinuria.

A century ago, Edmund Randerath (1899-1961), who was one of the pioneers in nephrology that provided indirect experimental proof for the glomerular origin of proteinuria, was born. In the first decades of this century, the concept prevailed that "nephrosis" was a process of primary tubular cell degeneration. In contrast to prevailing opinion, he interpreted these changes to be the result of the uptake and storage of serum proteins after they had been filtered in the glomerulus. Edmund Randerath proved the glomerular origin of proteinuria by astute experiments in amphibia. In the salamander, an intraperitoneal injection of albumin provoked the supposedly "degenerative" changes of tubular epithelial cells in only those nephrons that drained the coelomic cavity and were devoid of glomeruli, but not in those nephrons that were closed and attached to glomeruli. This observation provided incontrovertible evidence that the presence of serum proteins in tubular fluid was a prerequisite for the development of the tubular epithelial cell changes typically seen in nephrotic patients.

Five hundred years of the nephrotic syndrome: 1484-1984.

The nephrotic syndrome has emerged over several centuries as the consequence of continued profuse proteinuria, arising in turn from a variety of lesions affecting the glomerulus which impair glomerular ability to retain plasma proteins, in particular, albumin. As a syndrome, it has its own complications and requires its own management irrespective of the underlying lesions. Dissection of these by renal biopsy and by clinical investigation reveals a variety of systemic diseases which affect the kidney, but a majority of primary immune-based diseases appear unique to the glomerulus. Whether the lesion called by Müller and Munk 'nephrosis', and now called minimal change disease and focal segmental glomerulosclerosis is one disease or many, is the subject of intense debate at the moment, as is the relationship between two types of lesion. Only a better understanding of their pathogenesis, and of how the glomerulus normally retains plasma protein, will solve this knotty problem.

A notable case of nephrosis.

How a boy of 10 developed nephrosis more than 60 years ago, how he came to be seen by Sir Frederic Still with interesting later consequences, how his nephrosis cleared following measles, and how all this led to his becoming a distinguished paediatrician is told in a case history based on the diary kept by the boy's mother.

[The changing meaning of the term nephrosis since Noeggerath (author's transl)]. / Zum Wandel des Nephrose-Begriffs seit Noeggerath.

The term nephrosis has changed its meaning considerably since it was coined by Friedrich v. Müller. At the time of Noeggerath, whose 100 anniversary just has passed, nephrosis was defined by morphological terms describing various histological alterations of the renal tubuli which were considered to be degenerative. Today nephrosis is a clinical diagnosis, and usually called nephrotic syndrome. It is characterized by heavy proteinuria and hypoalbuminemia, and can be produced by various etiological causes. In pediatrics the most frequent type is lipoid nephrosis which is characterized by minimal glomerular lesions, negative immunofluorescence and steroid responsiveness. Patients with frequent relapses of lipoid nephrosis are difficult to handle by the physician, therefore the "International Study of Kidney Diseases in Children" and the "Arbeitsgemeinschaft für Pädiatrische Nephrologie" are conducting cooperative therapeutic trials, which results are mentioned briefly.